EU regulators slap safety restriction on Pfizer's Xeljanz

European safety regulators have placed restrictions on Pfizer’s Xeljanz, saying it should not be used in the higher dose in some patients with ulcerative colitis because of concerns of increased risk of blood clots on the lung and increased mortality.

Xeljanz (tofacitinib) is approved at the higher dose of 10 mg twice daily in patients with ulcerative colitis, although this can be reduced to 5 mg twice daily in patients who respond well.

But because of safety concerns, the PRAC is restricting prescription of Xeljanz, preventing new patients with ulcerative colitis and high risk of pulmonary embolism from starting on the drug.

In a safety alert published late last week, the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) said Pfizer had approached it in February with clinical trial data from a rheumatoid arthritis trial showing pulmonary embolism was almost six times more likely in patients treated with Xeljanz compared with a comparator arm treated with anti-TNF inhibitor drugs.

Xeljanz is not approved in rheumatoid arthritis in Europe at the higher dose, but is available in that dose in the US, and Pfizer’s data came from a cardiovascular post-marketing safety study required by the FDA as a condition of its licence.

Pfizer removed the 10 mg dose from the RA post-marketing study, codenamed A3921133, because of the safety issue.

The European agency’s PRAC has started to assess the increased risk of pulmonary embolism and increased mortality in patients treated with the drug, based on clinical data available in RA, and is to decide whether to maintain, vary, suspend, or revoke Xeljanz’s marketing authorisation in Europe as a result.

Once the PRAC has made its decision, it will pass this on to the CHMP senior scientific committee for ratification by the European Commission.

Xeljanz is also approved in the EU at a 5 mg twice daily dose in psoriatic arthritis, which is not affected by the safety issue for now.